Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1

Stoltz, D.A. et al. J. Clin. Invest. 118:3123–3131 (2008)

Speaker：連國廷                         Time：13:00~14:00, Nov. 19, 2008

Commentator：鄧景浩  老師              Place：Room 601

Abstract：

Pseudomonas aeruginosa, a gram-negative bacterium, is an important pathogen causing opportunistic infections in immunocompromised patients and those with cystic fibrosis. P. aeruginosa controls its gene expression, including that of virulence genes, in response to cell density by the quorum-sensing (QS) system, using N-3-oxododecanoyl homoserine lactone (3OC12-HSL) and N-butanoyl HSL (C4-HSL) as the QS signals (also called autoinducers) (1). PON1, a paraoxonase in liver and plasma, has the ability to hydrolyze paraoxon, lactone and organophosphates in mammals. The authors have found previously that PON1 can degrade 3OC12-HSL in vitro, however, they surprisingly found that the PON1 gene-knockout mice showed a reduced, instead of enhanced, mortality in P. aeruginosa infection. They later found that in the mouse deficient in PON1 the levels of two other paraoxonase family proteins, PON2 and PON3, were increased, making the interpretation of these data difficult in the PON1 gene-knockout mice (2). To clarify the role of PON1 in P. aeruginosa infection in vivo, the authors used the human PON1-transgenic Drosophila melanogaster, in which the functional human PON1 was expressed, as the model organism. They found that the virulence of P. aeruginosa in normal flies depended upon the production of 3OC12-HSL. On the other hand, the PON1-transgenic flies exhibited a reduced mortality after infection by P. aeruginosa. The reduced mortality was similar to the normal flies infected with the P. aeruginosa ΔlasI mutant (deficient in 3OC12-HSL production). They also demonstrated that the transgenic PON1 interferes with the expression of P. aeruginosa virulence gene by blocking the QS signaling systems. These results suggest that the lactonase might be important for the control of P. aeruginosa pathogenesis.

References：

1.      Dong, Y.H. and Zhang, L.H. 2005. Quorum sensing and quorum-quenching enzymes. J. Microbiol. 43:101–109.

2.      Ozer, E.A., et al. 2005. Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing. FEMS Microbiol. Lett. 253:29–37.